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Article

High-Spermidine-Producing Yeast Strain for Autophagy-Promoting Applications

by
Tomoyo Koshizawa
1,
Tomoe Numaguchi
1,
Masanori Tamakoshi
2,
Yuuki Sato
2,
Katsuyuki Hashimoto
1,
Nur Syafiqah Mohamad Ishak
1 and
Kazuto Ikemoto
1,*
1
Niigata Research Laboratory, Mitsubishi Gas Chemical Company, Inc., 182 Tayuhama, Kita-ku, Niigata 950-3112, Japan
2
Department of Life Science, Mitsubishi Gas Chemical Company, Inc., Mitsubishi building, 2-5-2 Chiyoda-ku, Tokyo 100-8324, Japan
*
Author to whom correspondence should be addressed.
Processes 2025, 13(10), 3141; https://doi.org/10.3390/pr13103141
Submission received: 26 August 2025 / Revised: 22 September 2025 / Accepted: 29 September 2025 / Published: 30 September 2025

Abstract

Polyamines, particularly spermidine, have emerged as key dietary factors with roles in cellular health, autophagy, and longevity. However, strategies for scalable production of polyamine-rich food ingredients remain limited. Here, we report the development of a high-spermidine-producing Saccharomyces cerevisiae strain, 3L63, obtained via ultraviolet mutagenesis of the K7 strain. This strain exhibited a 5.9-fold increase in the total polyamine content, with spermidine being the most abundant. A scalable fermentation system of up to 104 L was established, yielding a dried yeast product that met food safety criteria. Whole-genome sequencing identified mutations in central metabolic pathways, including ARG3, and functional enrichment analysis suggested broad metabolic rewiring, supporting an enhanced biosynthetic capacity, including polyamines. Free amino acid profiling revealed higher arginine levels in 3L63 than in K7, which is consistent with its role as a polyamine precursor. The 3L63 yeast-derived product was enriched in essential amino acids and polyamines. Functionally, this strain promoted the proliferation of normal and senescent human dermal fibroblasts, and its autophagy-inducing activity exceeded that of equivalent concentrations of pure spermidine, suggesting synergistic effects of yeast-derived bioactive compounds. This study demonstrates a non-genetically modified, high-spermidine yeast strain as a promising functional food ingredient with potential applications in healthy aging.
Keywords: polyamine; spermidine; yeast; autophagy; fermentation; food safety; metabolic engineering polyamine; spermidine; yeast; autophagy; fermentation; food safety; metabolic engineering

Share and Cite

MDPI and ACS Style

Koshizawa, T.; Numaguchi, T.; Tamakoshi, M.; Sato, Y.; Hashimoto, K.; Mohamad Ishak, N.S.; Ikemoto, K. High-Spermidine-Producing Yeast Strain for Autophagy-Promoting Applications. Processes 2025, 13, 3141. https://doi.org/10.3390/pr13103141

AMA Style

Koshizawa T, Numaguchi T, Tamakoshi M, Sato Y, Hashimoto K, Mohamad Ishak NS, Ikemoto K. High-Spermidine-Producing Yeast Strain for Autophagy-Promoting Applications. Processes. 2025; 13(10):3141. https://doi.org/10.3390/pr13103141

Chicago/Turabian Style

Koshizawa, Tomoyo, Tomoe Numaguchi, Masanori Tamakoshi, Yuuki Sato, Katsuyuki Hashimoto, Nur Syafiqah Mohamad Ishak, and Kazuto Ikemoto. 2025. "High-Spermidine-Producing Yeast Strain for Autophagy-Promoting Applications" Processes 13, no. 10: 3141. https://doi.org/10.3390/pr13103141

APA Style

Koshizawa, T., Numaguchi, T., Tamakoshi, M., Sato, Y., Hashimoto, K., Mohamad Ishak, N. S., & Ikemoto, K. (2025). High-Spermidine-Producing Yeast Strain for Autophagy-Promoting Applications. Processes, 13(10), 3141. https://doi.org/10.3390/pr13103141

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